The fundamental objective of this proposed research project is the delineation of the Gross passage A leukemogenic process. A three phase "step-by-step" analysis of dynamics in malignancy and immune system interaction will be carried out. In the first phase, malignancy induction data will be amplified by exploring additional viral dosages, routes of virus introduction, and preleukemic syngeneic organ graft effectiveness in the transmission of GPA leukemia both horizontally and vertically. The second phase will involve the determination of immunocompetence in the preleukemic and leukemic animal. Various parameters of the immune-response capacity will be measured: germinal center formation; antibody production; allograft rejection; graft-versus-host reactivity; and lymphocyte populations and reactivity. Additionally, the possibility that a thymus-peripheral node interaction exists during leukemogenesis will be explored. In the third phase, the host immune responses will be manipulated in attempts to immunize against, induce regression, or even complete rejection of GPA tumor. The discovery that syngeneic skin grafts can be made to reject under allograft influence provides the foundation for experiments in which alteration of malignancy induction by allografting will be ascertained. This delineation of the interaction between malignancy induction and immune system dynamics should significantly increase our understanding of leukemogenesis. Ultimately, information obtained from this study could be exploited to design new methods for control and prevention of malignancy in man.